Cerebrospinal Aβ11-x and 17-x levels as indicators of mild cognitive impairment and patients' stratification in Alzheimer's disease

• Published in: Translational psychiatry Vol. 3; no. 7; p. e281
• Main Authors: Abraham, J-D, Promé, S, Salvetat, N, Rubrecht, L, Cobo, S, du Paty, E, Galéa, P, Mathieu-Dupas, E, Ranaldi, S, Caillava, C, Crémer, G-A, Rieunier, F, Robert, P, Molina, F, Laune, D, Checler, F, Fareh, J
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 16.07.2013
• Subjects: Aged; Aged, 80 and over; Alzheimer Disease - cerebrospinal fluid; Amyloid beta-Peptides - cerebrospinal fluid; Biomarkers - cerebrospinal fluid; Case-Control Studies; Cognitive Dysfunction - cerebrospinal fluid; Cognitive Dysfunction - diagnosis; Female; Humans; Male; Middle Aged; Original; Peptide Fragments - cerebrospinal fluid; Severity of Illness Index
• ISSN: 2158-3188; 2158-3188
• DOI: 10.1038/tp.2013.58

In the present work, the concentrations of Aβ11-x and Aβ17-x peptides (x=40 or 42), which result from the combined cleavages of β-amyloid precursor protein (AβPP) by β'/α or α/γ-secretases, respectively, were assessed in cerebrospinal fluid (CSF) samples from patients with Alzheimer's disease (AD) or mild cognitive impairment (MCI). Specific multiplexed assays were set up using new anti-40 and anti-42 monoclonal antibodies (mAbs) for the capture of these N-truncated Aβ peptides and anti-11 or anti-17 mAbs for their detection. The specificity, sensitivity and reproducibility of such assays were assessed using synthetic peptides and human cell models. Aβ11-x and Aβ17-x were then measured in CSF samples from patients with AD (n=23), MCI (n=23) and controls with normal cognition (n=21). Aβ11-x levels were significantly lower in patients with MCI than in controls. Compared with the combined quantification of Aβ1-42, total Tau (T-Tau) and phosphorylated Tau (P-Tau; AlzBio3, Innogenetics), the association of Aβ11-40, Aβ17-40 and T-Tau improved the discrimination between MCI and controls. Furthermore, when patients with MCI were classified into two subgroups (MCI ≤1.5 or ≥2 based on their CDR-SB (Cognitive Dementia Rating-Sum of Boxes) score), the CSF Aβ17-40/Aβ11-40 ratio was significantly higher in patients with CDR-SB ≤1.5 than in controls, whereas neither Aβ1-42, T-Tau nor P-Tau allowed the detection of this subpopulation. These results need to be confirmed in a larger clinical prospective cohort.